The goal of this research is to develop new technology that would allow neuroscientists to investigate emergent properties in networks of hundreds of synaptically connected cortical neurons. Although many of the most important emergent properties of brains are predicted to arise in "local" networks involving a few hundred neurons, limitations in technology have largely prevented experiments in this regime. Work at the local network level is difficult because it requires high temporal and spatial resolution at hundreds of recording sites over durations of hours. Most approaches used today fail to meet all of these requirements because of long distances between recording sites, short recording durations, or low temporal resolution. Without new approaches to study activity at the local network level, we will be limited in our ability to determine the mechanisms that allow networks to produce important emergent properties, and in our ability to understand disorders like epilepsy and schizophrenia that have been hypothesized to involve disruptions at the local network level. The specific objective of this proposal is the development of a 512 microelectrode array system that can detect and manipulate emergent properties in cortical slice networks. We propose to accomplish this goal by pursuing three specific aims: (1) develop the existing software for a 60 electrode array so that it will identify neuronal avalanches and repeating activity patterns in data from the 512 electrode array; (2) develop a sterile recording chamber compatible with the 512 electrode array so that cortical slice cultures can be monitored for up to two weeks; and (3) develop the hardware and software necessary to deliver complex patterned stimulation through the 512 electrode array. Many scientists think that disorders such as epilepsy and schizophrenia are caused by disruptions in networks of cortical neurons. The proposed studies are expected to increase our understanding of how networks of neurons interact, and may therefore lead to new information that could help treat these and other disorders. [unreadable] [unreadable]